The greatest unsolved mystery of all is what consciousness is. Torday and Miller have hypothesized that consciousness is the homologous 'equivalent' of our physiology, behaving as our history, providing an algorithm by which evolution can determine how and why to adapt to ever-changing environmental conditions. Complicated physiology was reduced iteratively to the unicell by tracing the cell-cell signaling mechanisms that dealt with emergent threats based on Bayesian statistics. Unlike Darwinian random mutations, the current approach is predicated on structural and functional changes within the context of pre-existing physiologic traits. The cytoskeleton of the cell is a complete representation for all of the phases of life, past, present and future, controlling the Target of Rapamycin gene, which determines all of the stages of life-homeostasis, meiosis and mitosis. Viewed from this perspective, the cell remains at equipoise relative to the Singularity that existed before the Big Bang. The purpose of life is to collect epigenetic marks by pursuing energy flows, not conventional material change due to random mutations. The cytoskeleton universally controls all of the states of the cell - homeostasis, meiosis and mitosis, rendering the status of the cell relative to the prevailing circumstances. Indeed, the cytoskeleton of the cell is a central player in all of the phases of life, past, present and future. The above-described integration of physiology as the cipher for consciousness is quite ingenious as a 'top-down/bottom-up/middle-out' way of ensuring the holism of life and non-life. Recognition of the centrality of the cell has led to a number of novel insights into biology that have been represented by dogma up until now. Consequently, biology has been simplified by shifting from description to mechanism. Based on Ockam's Razor, the cellular approach to evolution is superior to Darwin.
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http://dx.doi.org/10.1016/j.pbiomolbio.2022.12.001 | DOI Listing |
Eur J Cancer
January 2025
JSC Biocad, St. Petersburg, Russia.
Background: Prolgolimab is an IgG1 anti-PD-1 monoclonal antibody with the Fc-silencing 'LALA' mutation. The phase III DOMAJOR study assessed efficacy and safety of prolgolimab in combination with pemetrexed and platinum-based chemotherapy vs placebo in combination with pemetrexed and platinum-based chemotherapy as first-line treatment for advanced non-small cell lung cancer (NSCLC).
Methods: 292 patients with advanced non-squamous NSCLC were randomized 1:1 to receive 4 cycles of pemetrexed, platinum-based drug and either prolgolimab (3 mg/kg Q3W) or placebo followed by prolgolimab/placebo with pemetrexed until disease progression or toxicity (≤36 months).
Int J Gynecol Cancer
January 2025
Nazionale dei Tumori di Milano, Fondazione IRCCS Istituto Gynecological Oncology Unit, Milan, Italy.
Objective: Endometrial cancers can be classified into 4 molecular sub-groups: (1) POLE mutated (POLEmut), (2) mismatch repair deficiency/microsatellite-instable (MMRd/MSI-H), (3) TP53-mutant or p53 abnormal (p53abn), and (4) no specific mutational profile (NSMP). Although molecular classification is increasingly applied in oncology, its role in guiding fertility-sparing treatments for endometrial cancer remains unclear. This study examines the prognostic role of molecular classification in fertility-sparing treatment and its potential to guide treatment decisions.
View Article and Find Full Text PDFBJUI Compass
January 2025
Division of Medical Oncology A Policlinico Umberto I Rome Italy.
Background: We present a systematic review and meta-analysis of randomized clinical trials (RCTs) with PARPi either as monotherapy or in combination with an androgen receptor-targeted agent (ARTA) in first- and second-line settings.
Methods: Primary endpoints are radiographic progression free survival (rPFS) and overall survival (OS) in patients with mCRPC and either unselected, homologous recombination repair wild-type (HRR-), homologous recombination repair mutated (HRR+) or with BRCA1, BRCA2, or ATM mutation. The effect of PARPi + ARTA in the second-line setting is also explored.
The expression of genomically-encoded information is not error-free. Transcript-error rates are dramatically higher than DNA-level mutation rates, and despite their transient nature, the steady-state load of such errors must impose some burden on cellular performance. However, a broad perspective on the degree to which transcript-error rates are constrained by natural selection and diverge among lineages remains to be developed.
View Article and Find Full Text PDFUltrason Imaging
January 2025
Department of Ultrasound, South China Hospital, Medical School, Shenzhen University, Shenzhen, China.
This study aims to establish and validate an ultrasound radiomics nomogram for preoperative prediction of central lymph node metastasis in papillary thyroid microcarcinoma (PTMC) before operation. A retrospective analysis conducted on ultrasonic images and clinical features derived from 288 PTMC patients, who were divided into training cohorts ( = 201) and validating cohorts ( = 87) in a ratio of 7:3 base on the principle of random allocation. Radiomics features were extracted from the PTMC patients after ultrasonic examination, followed by dimension reduction and characteristic selection to construct the radiomics score (Radscore) using LASSO regression analysis.
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